Fig. 4. Action potential firing of the axon initial segment hybrid neuron incorporating Nav1.2 variants in response to synaptic conductance input in DAPC experiments.
a Representative action potential firing elicited with ge/gi ratios of 1, 1.5, 2, 2.5, and 3 in the early-infantile (EI)-severe, EI-variable, EI-benign and later-onset (LO) groups. b–e Input–output relationships in the presence of Nav1.2 channel variants (WT, black solid circle; mutants, colored open circles) associated with EI-severe (b), EI-variable (c), EI-benign (d), or later-onset (LO) (e) SCN2A epilepsy. Two-way ANOVA, followed by Dunnett’s post-hoc test, was used to compare the AP firing frequencies elicited by scaled excitatory to inhibitory conductance ratios (ge/gi) in the presence of Nav1.2 variants; asterisks indicate P < 0.05 (see individual P values in Supplementary Table 7). Note the increased firing activity in the early-infantile severe/variable groups compared to wild-type, whereas later-onset variants result in an almost complete loss of firing. Data shown are mean ± SEM; n, the number of independent experiments between parentheses.